Methods and systems for optical imaging or epithelial luminal organs by beam scanning thereof

ABSTRACT

Arrangements, apparatus, systems and systems are provided for obtaining data for at least one portion within at least one luminal or hollow sample. The arrangement, system or apparatus can be (insertable via at least one of a mouth or a nose of a patient. For example, a first optical arrangement can be configured to transceive at least one electromagnetic (e.g., visible) radiation to and from the portion. A second arrangement may be provided at least partially enclosing the first arrangement. Further, a third arrangement can be configured to be actuated so as to position the first arrangement at a predetermined location within the luminal or hollow sample. The first arrangement may be configured to compensate for at least one aberration (e.g., astigmatism) caused by the second arrangement and/or the third arrangement. The second arrangement can include at least one portion which enables a guiding arrangement to be inserted there through. Another arrangement can be provided which is configured to measure a pressure within the at least one portion. The data may include a position and/or an orientation of the first arrangement with respect to the luminal or hollow sample.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is based upon and claims the benefit of priority fromU.S. patent application Ser. No. 60/761,004, filed Jan. 19, 2006, theentire disclosure of which is incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

The invention was made with the U.S. Government support under ContractNo. RO1CA103769 awarded by the National Institute of Health. Thus, theU.S. Government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates to methods and systems for opticalimaging, and more particularly to optically imaging epithelial luminalorgans by beam scanning thereof.

BACKGROUND OF THE INVENTION

Screening for diseases is a process whereby a person who is not known tohave one or more possible diseases undergoes a test to determine whetheror not the person has any such diseases. Screening is often conducted ona large population, and therefore is likely to be inexpensive andminimally-invasive. Surveillance of a patient with a particular diseaseis a test that is conducted on a person with the disease to determinethe severity of such disease, e.g., a degree of dysplasia in a patientwith a known pre-cancerous condition. Effective screening andsurveillance for the disease (e.g., dysplasia, cancer, etc.) ofepithelial luminal organs systems, such as that of the gastrointestinaltract, urinary tract, pancreatobiliary system, gynecologic tract,oropharynx, pulmonary system, etc. utilize a comprehensive evaluation ofa substantial portion of the mucosa. Certain beam scanning opticaltechniques, including time-domain optical coherence tomography (“OCT”),spectral-domain optical coherence tomography (“SD-OCT”), opticalfrequency domain imaging (“OFDI”), Raman spectroscopy, reflectancespectroscopy, confocal microscopy, light-scattering spectroscopy, etc.techniques have been demonstrated to provide critical information usablefor diagnosis of a mucosal disease, including dysplasia and earlycancer. However, these techniques are considered point-scanning methods,which are generally capable of obtaining image data only at one locationat a time. In order to comprehensively screen large luminal organs, afocused beam can be rapidly scanned across the organ area of interest,e.g., over a large area, while optical measurements are obtained.Catheters, probes, and devices capable of performing this beam scanningfunction, are therefore generally used for an appropriate application ofthese and other optical technologies for screening large mucosal areas.

The screening described above should also be inexpensive so as to permittesting of a large population. In order to reduce the cost of screening,it may be preferable to provide a device or systems that is capable ofbeing operated in a stand alone imaging mode. Such stand-alone imagingcan be conducted in unsedated patients, which significantly lowers thecost of the procedure and the complication rate relative tovideoendoscopy. For surveillance, the comprehensive imaging procedurecan be utilized to direct biopsies to the locations that contain themost severe disease. Since both the imaging and the intervention mayoccur during the same imaging session, the comprehensive imaging andinterpretation of large volumetric data sets should be accomplished in ashort amount of time.

Certain challenges exist when using scanned, focused light tocomprehensively image luminal organs. Focused spots generally remain infocus for a certain range of distances from the probe to the tissuesurface. For certain organ imaging systems, this focal distance (e.g.,one metric of which is the Rayleigh range) is significantly smaller thanthe diameter of the luminal organ. As a result, screening the luminalorgan mucosae typically is done by centering the distal/focusing opticsof the imaging probe within the organ lumen so that the beam remains infocus throughout the comprehensive scan. Conventional systems employinga centering balloon have been described for OCT imaging of theesophagus. (See G. Tearney, “ Improving Screening and Surveillance inBarrett's Patients,” NIH Grant No. R01-CA103769; and Boppart et al.,“Optical Coherence Tomography: Advanced Technology for the EndoscopicImaging of Barrett's Esophagus,” Endoscopy 2000; 32 (12), pp. 921-930).

Prior clinical studies are known to have acquired images likely onlyfrom discrete esophageal locations. The use of such conventional devicesused an endoscopic guidance arrangement to identify regions of interestalong the esophageal wall, and to direct the imaging probe to theselocations. Certain components of the arrangement to providehigh-resolution scanning of the focused beam should be considered. Foreach organ system, a certain catheter/probe types and modes of entryinto the patient may be desirable for a less invasive operation.Different centering mechanisms are possible and designs are specific tothe anatomy. The beam scanning probe optics should be positioned to thearea of interest prior to conducting the imaging without an expensive orcomplex intervention. The beam focusing mechanism should contain anarrangement for correcting for aberrations caused by the probesheath/centering mechanisms. In order to obtain accurate large area two-and three-dimensional images of the organ, the position of the beamshould be known with precision for each data acquisition point.

Accordingly, there is a need to overcome the deficiencies describedherein above.

OBJECTS AND SUMMARY OF THE INVENTION

To address and/or overcome the above-described problems and/ordeficiencies, exemplary embodiments of arrangements and processes can beprovided that for optical imaging of epithelial luminal organs by beamscanning thereof. These exemplary embodiments of the arrangements andprocess can utilize a probe and/or disposable portion thereof or ofanother device which can utilize the following elements and/componentsfor optical imaging of epithelial luminal organs by beam scanning. Inparticular, these exemplary embodiments can utilize one or more opticalwaveguides, one or more optics at the distal end to focus the beam, oneor more optics at the distal end to redirect the beam, one or moreoptics at the distal end to correct for optical aberrations, one or morearrangements for scanning beam across the luminal organ surface, acentering mechanism, and a guidewire apparatus.

Thus, in accordance with one exemplary embodiment of the presentinvention, Arrangements, apparatus, systems and systems are provided forobtaining data for at least one portion within at least one luminal orhollow sample. The arrangement, system or apparatus can be (insertablevia at least one of a mouth or a nose of a patient. For example, a firstoptical arrangement can be configured to transceive at least oneelectromagnetic (e.g., visible) radiation to and from the portion. Asecond arrangement may be provided at least partially enclosing thefirst arrangement. Further, a third arrangement can be configured to beactuated so as to position the first arrangement at a predeterminedlocation within the luminal or hollow sample. The first arrangement maybe configured to compensate for at least one aberration (e.g.,astigmatism) caused by the second arrangement and/or the thirdarrangement. The second arrangement can include at least one portionwhich enables a guiding arrangement to be inserted there through.

According to another exemplary embodiment of the present invention,another arrangement can be provided which is configured to measure apressure within the at least one portion. The data may include aposition and/or an orientation of the first arrangement with respect tothe luminal or hollow sample. The further arrangement can include ascanning arrangement, the further arrangement detecting the position andthe rotation angle by digital counting of encoder signals obtained fromthe scanning arrangement during at least one scan of the at least onesample. An additional arrangement can be provided which is configured toreceive the position and the rotational angle, and generate at least oneimage associated with the portion using the position and the rotationalangle. The additional arrangement may be further configured to correctat least one spatial distortion of the at least one image.

In another exemplary embodiment of the present invention, a processingarrangement may be provided which is capable of being controlled toreceive a plurality of images of the sample during at least two axialtranslations of the first arrangement with respect to the sample. Eachof the axial translations may provide at a rotational angle. The datacan be interferometric data associated with the sample. Theinterferometric data may be spectral-domain optical coherence tomographydata, time-domain optical coherence tomography data and/or opticalfrequency domain imaging data.

These and other objects, features and advantages of the presentinvention will become apparent upon reading the following detaileddescription of embodiments of the invention, when taken in conjunctionwith the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present invention willbecome apparent from the following detailed description taken inconjunction with the accompanying figures showing illustrativeembodiments of the present invention, in which:

FIG. 1 is a schematic and separated-parts diagram of an exemplaryembodiment of a micro-motor catheter according to the present inventionwhich can exclude include a centering mechanism;

FIG. 2 is a visual image of a linear push-pull catheter that may achieveonly a limited large area imaging of a target area of an anatomicalstructure;

FIG. 3 is a general schematic diagram of an exemplary embodiment of thearrangement according to the present invention, which can includeguidewire provision, aberration correction optics, centering mechanism,and rapid beam scanning mechanisms with feedback;

FIG. 4 is a schematic diagram of an exemplary embodiment of an imagingcatheter of the arrangement shown in FIG. 3 in use at a target area ofan anatomical structure;

FIG. 5 is a block and flow diagram of exemplary electrical and dataconnections between components of a control and data-recording mechanismof the exemplary arrangement according to the present invention shown inFIG. 4, including data acquisition and control unit, imaging data, probescanner motor controllers, and probe scanner motors;

FIG. 6 is a schematic diagram illustrating an exemplary embodiment of aprocess according to the present invention which enables data to beacquired by the data acquisition unit shown in FIG. 5, and can provideprobe position for each measured a-line;

FIG. 7A is an illustration of an exemplary embodiment of a probescanning method according to the present invention in which the beam isrotated in an accelerated manner, and slowly displaced axially to createa spiral imaging pattern;

FIG. 7B is an illustration of an exemplary embodiment of a probescanning method in which the beam is scanned axially in an acceleratedmanner, and then repositioned rotationally and repeated;

FIG. 8A is a schematic/operational illustration of a first exemplaryembodiment of a rapid exchange balloon catheter according to the presentinvention which includes the guidewire provision located at the tip;

FIG. 8B is a schematic/operational illustration of a second exemplaryembodiment of the rapid exchange balloon catheter according to thepresent invention which includes the guidewire provision located at thetip as a secondary channel;

FIG. 8C is a schematic/operational illustration of a third exemplaryembodiment of a rapid exchange balloon catheter according to the presentinvention which includes the guidewire provision located prior to theballoon as a secondary channel;

FIG. 9A is an exploded view of the use of an exemplary embodiment of anover-the-wire balloon catheter according to the present invention duringthe insertion of a guidewire;

FIG. 9B is an exploded view of the use of the exemplary embodiment ofthe over-the-wire balloon catheter according to the present inventionduring the placement of a balloon catheter over the guidewire;

FIG. 9C is an exploded view of the use of the exemplary embodiment ofthe over-the-wire balloon catheter according to the present inventionduring the removal of the guidewire;

FIG. 9D is an exploded view of the use of the exemplary embodiment ofthe over-the-wire balloon catheter according to the present inventionduring the placement of optics in the balloon;

FIG. 10 is a schematic diagram of an exemplary embodiment of a balloonarrangement according to the present invention which uses two sheathsand guiding the inflation material (e.g., air or saline) from aninflation channel at the distal portion to the balloon between thesesheaths;

FIG. 11 is a schematic diagram of an exemplary embodiment of a ballooncatheter which allows the imaging window to contain a single sheath;

FIG. 12 is side and front views of a schematic diagram of an exemplaryembodiment of probe optics according to the present invention whichincludes aberration correction optics (e.g., a micro-cylindrical lens);

FIG. 13 is a schematic side view of another exemplary embodiment of aballoon catheter according to the present invention which uses abackward facing in-catheter motor to rotate the imaging beam;

FIG. 14 is a schematic side view of yet another exemplary embodiment ofthe balloon catheter according to the present invention which uses aforward facing in-catheter motor to rotate the imaging beam;

FIG. 15 is a schematic side view of an exemplary variant of the ballooncatheter shown in FIG. 14 modified to allow a motor position measurement(e.g., encoder) signal to be generated;

FIG. 16A is a block diagram of an exemplary embodiment of a systemaccording to the present invention configured to adjust the referencearm delay in response to the measured balloon position in order to keepthe tissue in the system imaging range;

FIG. 16B is a graph of the output of the system of FIG. 16A which isprovided as a graph of reflectivity versus depth;

FIG. 17A is a general illustration of an exemplary embodiment of a pillon a string arrangement according to the present invention in which animaging unit is swallowed by a patient, and connected by a “string”containing optical fiber and/or electrical connections to the imagingunit;

FIG. 17B is an illustration of the arrangement of FIG. 17A in operationwhile being swallowed by the patient;

FIG. 17C is a schematic detailed diagram of the arrangement of FIG. 17A;

FIG. 18A is an illustration of a trans-oral placement of an exemplaryembodiment of the catheter according to the present invention;

FIG. 18B is an illustration of a trans-nasal placement of an exemplaryembodiment of a trans-oral catheter according to the present invention;

FIG. 19A is a schematic diagram of an exemplary embodiment of a wirecage centering arrangement according to the present invention in aclosed mode;

FIG. 19B is a schematic diagram of an exemplary embodiment of the wirecage centering arrangement according to the present invention during theopening starting from a distal portion thereof;

FIG. 20 is a block diagram of an optical coherence tomography screeningdevice combined with a further optical imaging arrangement operating ata second wavelength band according to an exemplary embodiment of thepresent invention;

FIG. 21 is a block diagram an optical coherence tomography imagingsystem configured to allow a combination of an ablation beam with theimaging beam in a sample arm in accordance with another exemplaryembodiment of the present invention;

FIG. 22 is a block diagram an optical coherence tomography imagingsystem configured to allow an on-the-fly ablation in accordance with yetanother exemplary embodiment of the present invention;

FIG. 23A is a flow diagram of an exemplary embodiment of a process forablation marking according to the present invention for the on-the-flyablation;

FIG. 23B is a flow diagram of an exemplary embodiment of a process forablation marking according to the present invention for stopping andablating;

FIG. 24 is an endoscopic image showing the visibility of ablation marksin a swine esophagus for imaging by the exemplary embodiments of thearrangements and processes according to the present invention;

FIG. 25A is a block diagram of an exemplary embodiment of thearrangement according to the present invention including an ablationlaser source which uses multiple lasers of wavelengths in the 1400-1499nm range that are multiplexed together with an optical switch as ashutter, with the optical switch after the multiplexer (MUX);

FIG. 25B is a block diagram of the exemplary embodiment of thearrangement according to the present invention including an ablationlaser source which uses multiple lasers of wavelengths in the 1400-1499nm range that are multiplexed together with an optical switch as ashutter, with separate optical switches for each laser located beforethe multiplexer (MUX);

FIG. 26 is a flow diagram of an exemplary process performed by animaging system according to the present invention which marks areas ofinterest identified in a completed imaging session;

FIG. 27 is a flow diagram of an exemplary procedure for placement ofexemplary embodiments of the over-the-wire catheter or therapid-exchange catheter according to the present invention;

FIGS. 28A-C are illustrations of multiple probe placements to image overan area larger than the area of the imaging window of the probe invarious stages in accordance with an exemplary embodiment of the presentinvention;

FIG. 29 is a flow diagram of an exemplary placement procedure accordingto the present invention in which the balloon is inflated in the stomachand pulled back until resistance is encountered, thereby locating theproximal end of the balloon with a Gastroesophageal junction; and

FIGS. 30A-30C are the exemplary steps performed by the exemplaryarrangement using the exemplary method of FIG. 29.

Throughout the figures, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components or portions of the illustrated embodiments. Moreover, whilethe subject invention will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments. It is intended that changes and modifications can be madeto the described embodiments without departing from the true scope andspirit of the subject invention as defined by the appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

An exemplary embodiment of a prototype esophageal probe 1 in accordancewith the present invention was constructed to investigate thefeasibility of obtaining images of the entire distal esophagus, theschematic diagram of this exemplary probe is illustrated in FIG. 1. Suchexemplary prototype esophageal screening probe 1 was designed to enableacquisition of images of the entire distal esophagus while operatingindependently of endoscopy, in standalone mode. Imaging of the entiredistal esophagus, however, can be a challenging task as the distancebetween the catheter and the esophageal wall may vary significantly,even under optimal conditions. Since the Rayleigh range over which theimages remain in focus is approximately 1 mm (˜35 μm spot diameter), theesophageal lumen should be made as circular as possible, and the probeshould generally be centered within the esophageal lumen.

In such exemplary prototype screening probe 1, an esophageal ballooncentering catheter (e.g., Eclipse 18×8, Wilson-Cook Medical, Inc.) wasused to achieve these tasks. The probe incorporated an inner corecontaining an optical fiber. The fiber terminated at the distal end ofthe inner core and the light was focused by a miniature gradient index(GRIN) lens and redirected onto the esophageal surface by a microprismas shown in FIG. 1. The inner core was inserted into the central lumenof the balloon catheter (as also shown in FIG. 1). Using this probe,volumetric images of the distal esophagus were obtained by, rapidlyrotating the inner core to obtain circumferential cross-sectional imageswhile translating the inner core longitudinally. Volumetric data of a 2cm diameter porcine esophagus was obtained ex vivo over a longitudinalextent of 3 cm using the prototype probe. Single longitudinal- andcross-sections of the 3D data set demonstrate the capability of thisdevice to obtain high-resolution images throughout the volume. Byacquiring images at a rate of 4 frames per second with a pullbackvelocity of 100 μm per second, the entire volumetric data set wasobtained in 5 minutes (see FIG. 2). This exemplary prototype accordingto the present invention demonstrated that a small-diameter OCT probecan be constructed to obtain high quality and high-resolution images ofthe entire distal esophagus.

An exemplary embodiment of an apparatus for performing large-areaimaging of epithelial luminal organs by beam scanning according to thepresent invention can be provided. Such exemplary embodiment of theapparatus can include an imaging system, an imaging catheter, andcatheter scanner. The imaging system delivers light to the imagingcatheter and recovers the light returning from the catheter to generatethe image. The imaging catheter directs the light generated by theimaging system to the luminal organ, and focuses this light as a beamdirected at the organ luminal surface. The catheter scanner is used todirect the scanning of this beam across a large area of the luminalsurface.

FIG. 3 shows a general schematic diagram of an exemplary embodiment ofan arrangement according to the present invention which can include animaging system.

The imaging system can include an optical frequency domain imaging(“OFDI”) system 100 (e.g., as described in International PatentApplication PCT/US2004/029148, filed Sep. 8, 2004), the catheter scanneris a rotary fiber optic coupler with pullback 110 (e.g., as described inU.S. patent application Ser. No. 11/266,799, filed Nov. 2, 2005), andthe imaging catheter is a balloon catheter probe 120. OFDI is ahigh-speed imaging technology which is similar to optical coherencetomography (“OCT”). The imaging system 100 shown in FIG. 3 can also be aspectral-domain optical coherence tomography (“SD-OCT”) system (e.g., asdescribed in U.S. patent application Ser. No. 10/501,276, filed Jul. 9,2004) or a time-domain optical coherence tomography (“TD-OCT”) system.The light from the imaging system 100 can be directed to the catheterscanner 110 which can be a part of a balloon imaging catheter 120.

FIG. 4 shows a schematic diagram of an exemplary embodiment of theballoon imaging catheter 120 of the arrangement shown in FIG. 3 in useat a target area of an anatomical structure. For example, the catheterscanner 110 may provide light (or other electromagnetic radiation) to aninner core 125 which can be enclosed by optically transparent sheaths130. At a distal end of the inner core 125, focusing optics 140 canfocus and direct the light to the surface of a luminal organ 145 to beimaged. A balloon 135 can be inflated to a center the inner core 125 inthe organ 145. The inner core 125 can be configured to rotate andtranslated axially through the catheter scanner 110, which allows theimaging beam to be scanned over a large area of the organ 145. The innercore 125 can include a fiber optic cable that may guide this light tothe distal end of the inner core 125. By recording the signal (e.g., theOFDI signal) as the beam is scanned, a large area of the luminal organ145 can be imaged.

FIG. 5 a block and flow diagram of exemplary electrical and dataconnections between components of control and data-recording mechanismthe exemplary arrangement according to the present invention shown inFIG. 4. The flow of the data, signals and/or information as shown inFIG. 5 allows the beam position to be recorded simultaneously with therecording of the imaging data to allow for, e.g., a substantially exactspatial registration of the imaging data. As shown in FIG. 5, theimaging data obtained by the OFDI system can be acquired by a dataacquisition and control unit 210. The catheter scanner 110 can achievebeam scanning by using a motor 240 provided for rotation and a motor 250provided for pullback. Each motor 240, 250 can be controlled by a motorcontroller 220, 230, respectively, in a closed loop operation. The dataacquisition and control unit 210 can command the motor controller units220, 230 to achieve certain motor velocities and/or positions. Theencoder signals forwarded from the motors 240, 250 can be configured tobe available to both the motor controller units 220, 230 and the dataacquisition and control unit 210. As such, each time a depth scan isacquired on the imaging data input, the encoder signals can be recordedfor each motor 240, 250, and thus approximately the exact beam positionfor that depth scan can be recorded.

FIG. 6 shows a schematic diagram illustrating an exemplary embodiment ofa process according to the present invention which enables data to beacquired by the data acquisition unit 210 shown in FIG. 5, and provide aprobe position for each measured a-line. For example, a trigger signal300 can be used to trigger a single acquisition of a depth scan on ananalog to digital (A-D) converter 311, and also to record the value of adigital counter 321 and a digital counter 331 capable of receiving tothe rotary motor encoder signal 320 and pullback motor encoder signal330, respectively. The encoder signals 320, 330 can be TTL pulse trainswhich may switch at a defined rate per motor revolution. Thus, bycounting these switches using digital counters, the current motorpositions can be measured. The A-D converter 311 and digital counters321, 331 can be contained in the data acquisition unit 340.

FIG. 7A shows an illustration of an exemplary embodiment of a probescanning method 350 according to the present invention in which the beamis rotated in an accelerated manner, and slowly displaced axially tocreate a spiral imaging pattern. For example, the rotational scanningcan occur as a first priority, and the axial (e.g., pullback) scanningcan occur as a second priority. This may result in a helical dataset.

FIG. 7B shows an illustration of another exemplary embodiment of theprobe scanning method 360 according to the present invention in whichthe beam is scanned axially in an accelerated manner, and thenrepositioned rotationally and repeated. In (B), axial (pullback)scanning occurs as a first priority and rotational scanning as thesecond priority. Because the imaging quality may be best when viewedalong the first scan priority, the choice of the scan priority candepend on whether transverse (rotational) images or axial images areneeded.

FIG. 8A is a schematic/operational illustration of a variant of theexemplary embodiment of a rapid exchange balloon catheter 120 asdescribed above with reference to FIG. 3 which includes the guidewireprovision located at the tip. In this exemplary embodiment, it ispossible to include a rapid-exchange placement thereof over a guidewire.In particular, for the rapid-exchange placement, a guidewire 400 can befirst placed in the organ to be imaged, and the catheter may then bethreaded along the guidewire 400. This exemplary technique according tothe present invention makes the placement of the catheter significantlyeasier in a number of applications. For example, as shown in FIG. 8A, aguidewire provision can be located by placing a through-hole 410 in thedistal end of the sheath of the balloon catheter 120. FIG. 8B shows aschematic/operational illustration another exemplary variant of therapid exchange balloon catheter 120 according to the present inventionwhich includes a guidewire provision is located by attaching a secondtube 420 to the distal end of the balloon catheter 120. FIG. 8C shows aschematic/operational illustration yet another exemplary variant of therapid exchange balloon catheter 120 according to the present invention,in which a tube 430 is located on the proximal side of the balloon.

FIGS. 9A-9D are exploded views of the use of an exemplary embodiment ofan over-the-wire balloon catheter which uses a guidewire 510 in acentral lumen thereof according to the present invention during theinsertion of a guidewire. In FIG. 9A, the guidewire 510 is placed in theorgan 500. Then, in FIG. 9B, the catheter is threaded over the guidewire510 such that the guidewire 510 is enclosed in the center lumen 520 ofthe catheter. The guidewire 510 is then removed in FIG. 9C. Further, inFIG. 9D, inner core optics 530 are threaded down the catheter centerlumen 520, and imaging is initiated.

FIG. 10 shows a side view of a schematic diagram of an exemplaryembodiment of a balloon catheter which includes a device 600 that can beused to inflate the balloon. For example, the pressure of the balloon650 may be monitored using a manometer 620. This pressure can be used tooptimize the inflation of the balloon 630, as well as assess theplacement of the catheter by monitoring the pressure of the organ.

FIG. 11 shows a schematic diagram of an exemplary embodiment of aportion of a balloon catheter which allows the imaging window to containa single sheath. For example, the balloon 700, its proximal attachment720 and its distal attachment 710 to a catheter inner sheaths 705 areshown in this figure. In the distal attachment 710 shown in detail insection B, a hole in the sheath 715 can be included to accept aguidewire for use in rapid-exchange catheters (as described above andshown in FIGS. 8A-8C). The balloon 700 can be attached to the innersheath 722, which extends over the extent of the balloon. The details ofthe proximal attachment 720 of the balloon 720 are shown in section C.The balloon 720 attaches to an outer sheath 721, which terminatesshortly after entering the balloon 720. This outer sheath 721 can bebonded to the inner sheath 722. Two holes 724 and 725 may be provided inthe outer sheath 721 such that the balloon can be inflated through thechannel created by the inner and outer sheaths 721, 722. One of theexemplary advantages of this exemplary design of the balloon catheter isthat there is a single sheath extending along and in the majority of theballoon 720. Because these sheaths may introduce aberrations in theimaging beam and degrade imaging quality, the ability to have oneinstead of two sheaths in the balloon can improve image quality.

FIG. 12 shows side and front sectional view of focusing optics at thedistal end of an inner core of an exemplary embodiment of the catheteraccording to the present invention. The light or other electromagneticradiation provided via an optical fiber 830 can be expanded and focusedby a GRIN 840 lens. The focal properties of this lens 840 may beselected to place the focal point of the beam near the organ lumen. Amicro-prism 850 can reflect the beam by approximately 90 degrees. Asmall cylindrical lens 860 may be attached to the micro-prism 850 tocompensate for the astigmatism of the beam induced by sheaths 800 and810. Alternately, the micro-prism 850 itself can be polished to have acylindrical curvature on one side to achieve this astigmatismcorrection.

FIG. 13 is a schematic diagram of an exemplary implementation andanother exemplary embodiment of the arrangement according to the presentinvention, e.g., beam scanning in the exemplary balloon catheter probe.In particular, the rotational scanning can be achieved by placement of amicro-motor 930 inside the catheter itself. As shown in FIG. 13, themotor 930 can be placed at the distal end of the catheter, and theoptical fiber 950 may be directed to a prism 960 mounted on the motorshaft 965. Exemplary electrical connections 940 to the motor 930 can bepassed through the imaging path to the motor 930, possibly causing aslight obstruction of the imaging beam. A balloon can be used to centerthis optical core in the luminal organ. A cylindrical lens or otherastigmatism correction optics 970 may be provided on or at the prism tocompensate for astigmatic aberrations caused by passage through atransparent sheath 900. Axial scanning can be achieved by translation ofthe entire optical core, including the focusing optics and the motor 930within the catheter transparent sheath 900. This translation may beaffected by a pullback device at the distal end of the catheter.

FIG. 14 shows an exemplary embodiment of a catheter according to thepresent invention which is similar to that of FIG. 13, but modified byprevent blocking of the imaging beam by motor electrical connections. Inthis exemplary embodiment, an optical fiber 1000 can be directed past amotor 1010, and reflected by a reflection cap 1080 toward a micro-prism1050 mounted on a motor shaft 1055. An aberration correcting optic 1060can be provided on or at the prism 1050. The entire device can betranslated to achieve axial scanning.

FIG. 15 shows a side view of yet another exemplary embodiment of acatheter which is similar to that of FIG. 14, but modified to allow fora usage of an additional optical signal which can be used as a motorencoder signal. In this exemplary embodiment, a second optical fiber1100 directs the light or other electromagnetic radiation past the motor1100. This light/radiation can be focused and reflected by optics 1110toward a reflective encoder 1120, which may be located on a motor driveshaft 1111. The reflective encoder 1120 can include alternate areas ofhigh and low reflectivity. As the motor shaft 1111 rotates, the lightreflected into this fiber may varies according to information providedby the encoder 1120. By detecting the reflected optical power, theposition, velocity, and direction of rotation of the motor 1100 can bemeasured. This information can be used to control the motor 1100 and/orto register the image with the beam position.

FIG. 16A is a block diagram of an exemplary embodiment of a system(e.g., an OCT system) according to the present invention configured toadjust the reference arm delay in response to the measured balloonposition in order to keep the tissue in the system imaging range. Thisexemplary OCT imaging system can implement auto-ranging. For example, inOCT, OFDI, or SD-OCT systems, the reflectivity can be measured over alimited depth range. If the sample is not located within this depthrange, it generally may not be measured. The balloon catheter can centerthe optical probe in the lumen, and thus maintain the organ luminalsurface at approximately a constant depth (balloon radius) from theprobe. However, if this is imperfect due to pressure on the balloondistorting its shape, the organ can fall outside the imaging range. Inthe exemplary embodiment shown in FIG. 16A, the auto-ranging can be usedto adjust the imaging depth range to track the position of the luminalorgan. This can be effectuated by locating the position 1210 of thesurface of the sample (e.g., the balloon surface) by its largereflectivity signal (as shown in FIG. 16B), and adjusting the referencearm delay 1220 to reposition the imaging range accordingly. Thereference arm adjustment can involve a modification of the reference armoptical path delay.

FIGS. 17A and 17C show illustrations of an exemplary embodiment of a“pill-on-a-string” arrangement according to the present invention inwhich an imaging unit is swallowed by a patient, and connected by a“string” 1310 containing optical fiber and/or electrical connections toan imaging probe 1300, For example, the imaging probe 1300 (e.g.,“pill”) containing a micro-motor 1320 is swallowed by the patient (seeFIG. 17B). The exemplary micro-motor shown in FIG. 14 can be used as themotor 1320. The probe 1300 can be connected to the system by a “string”1310 containing fiber optic and electrical connections. By using this“string” 1310, the position of the probe 1300 can be controlled, and theprobe 1300 may be placed, for example, in the esophagus of a patient.After imaging, the probe 1300 can be retrieved using this “string”1310.

FIGS. 18A and 18B show illustration of trans-oral placement andtrans-nasal placement, respectively, of an exemplary embodiment of thecatheter according to the present invention, e.g., for the uppergastro-intestinal tract imaging. In FIG. 18B, the catheter 1410 can beplaced through the mouth 1400, i.e. trans-orally. In FIG. 18B, thecatheter 1410 may be placed through the nasal orifice 1420, i.e.trans-nasally. Trans-nasal designs can have the advantage of notrequiring patient sedation, but should be small in diameter. Arelatively small size of the fiber optical imaging core according to theexemplary embodiment of the present invention can allow for itsimplementation trans-nasally.

FIGS. 19A and 19B show schematic diagrams of an exemplary embodiment ofa wire cage centering arrangement of an exemplary catheter according tothe present invention in a closed mode, and during the opening startingfrom a distal portion thereof, respectively. For example, the cathetermay use wire strands instead of a balloon to expand and center the inneroptical core in the luminal organ. The catheter can include an outersheath 1510, a set of expandable wire stents 1500 and an inner core1530. After the placement of the catheter, the other sheath may beretracted to allow the wire stenting 1500 to expand the organ. Afterimaging, the outer sheath 1510 may be extended to collapses the wirestenting, and the catheter can be removed.

FIG. 20 illustrates a block diagram of an exemplary embodiment of animaging system according to the present invention in which a secondwavelength band can be multiplexed into the catheter to achieve a secondimaging modality. This modality could, for example, be visible lightreflectance imaging or fluorescence imaging. In this exemplaryarrangement, a visible light source 1600 can be coupled to the imagingcatheter (e.g., as the one shown in FIG. 3) via a wavelength divisionmultiplexer 1630 which combined the second wavelength band with aprimary imaging wavelength band, e.g., typically infrared. The visiblelight reflected from the sample can be separated from a primary imagingwavelength band by this wavelength division multiplexer 1630, anddirected toward a photoreceiver 1620 by a splitter 1610.

An advantageous additional functionality for an epithelial luminal organimaging system can be a capability to direct subsequent inspection to aregion of interest identified in the imaging dataset. For example, if anarea of dysplasia is detected in a region of the esophagus, one mightwant to direct an endoscope to take a tissue biopsy in that area toconfirm that diagnosis. A method and system can be used for placing avisible mark on the tissue at a location of interest identified in theimage dataset. FIG. 21 shows a block diagram of still another exemplaryembodiment of the arrangement according to the present invention forachieving this by the coupling of an ablation laser 1700 through a fiberoptic wavelength division multiplexer 1710 to the imaging catheter. Theablation laser 1700 can be configured to include an optical power andwavelength sufficient to create superficial lesions on the luminalorgan. These lesions can be seen endoscopically, and may be used asmarkers for further investigation, e.g., biopsy. As shown in FIG. 21,the catheter can point to an area to be marked and made stationary.

The ablation laser is then turned on for a duration sufficient to createthe visible lesion.

FIG. 22 shows an alternate exemplary embodiment of the arrangementaccording to the present invention in which the catheter scanner is notstopped but instead ablation is performed on-the-fly. The dataacquisition unit 1720 is programmed to open an optical shutter 1730 whenthe catheter is pointed at the region of interest. The optical shutter1730 can transmit the ablation light when open, and blocks in whenclosed. For example, the catheter can remain in motion.

FIG. 23A shows a flow diagram of an exemplary embodiment of a processfor ablation marking according to the present invention for theon-the-fly ablation in the area of interest. In particular, a point tooblate is identified in step 1810. In step 1820, the shutter is set toopen at such point. In step 1830, the shutter and ablation laser isenabled, and then, in step 1840, the shutter and/or the ablation laseris disabled.

FIG. 23B shows a flow diagram of an exemplary embodiment of a processfor ablation marking according to the present invention for stopping andablating in the are of interest. In particular, a point to oblate isidentified in step 1850. In step 1860, catheter is commanded to stop atthat point. In step 1870, the shutter and ablation laser is enabled, andthen, in step 1880, the shutter and/or the ablation laser is disabled.The spinning of the catheter is restarted in step 1890.

FIG. 24 shows an exemplary image (generated using the exemplaryembodiments of the present invention) which includes ablation markingregions of interest. For example, the ablation marks 1900 are shownwhich are created in the esophagus using a series of lasers ofwavelengths 1440 nm to 1480 nm and an optical power of approximately 300mW for a duration of approximately 1 second.

FIGS. 25A and 25B show flow and block diagrams of interconnections of anexemplary embodiments of the arrangement according to the presentinvention, and implementations of an exemplary method of the presentinvention which can combining multiple ablation lasers and an opticalswitch (shutter) of the exemplary arrangement. In FIG. 25A, multiplelasers 2000, 2010, and 2020 can be combined using a multiplexer (MUX)2030, which can be a wavelength-division multiplexer, a polarizationmultiplexer, and/or a combination of both, followed by a single shutter2040. In FIG. 25B, each laser 2000, 2010, 2020 can use a separateshutter 2050, 2060, 2070, which may be subsequently combined using a MUX2080.

FIG. 26 shows a block diagram of an exemplary embodiment of a method forexamining a luminal organ and subsequent marking of areas of interest.In step 2100, the hale area is imaged in full. Then, in step 2110, areasof interest are identified using either automated algorithms orinspection by an operator. In step 2120, the catheter is directed to thearea of the first region of interest. Imaging is optionally commencedand the catheter position is adjusted interactively to re-find theregion of interest in step 2130. This re-finding procedure cancompensate for displacement of the catheter due to, for example,peristaltic motion in the esophagus. Next, in step 2140, a single orseries of ablation marks can be made adjacent to or around the region ofinterest. This procedure is repeated for each of the areas of interest(steps 2150, 2130, 2140, and so on). In step 2160, the catheter is thenremoved and additionally inspection or biopsy is performed as thosemarked areas in step 2170.

FIG. 27 shows an exemplary embodiment of a procedure according to thepresent invention for placement of the imaging catheter using endoscopicplacement of the guidewire. In particular, the guidewire is insertedthrough an endoscope channel in step 2200. In step 2210, the endoscopeis then removed, leaving the guidewire. In step 2220, the catheter isplaced over the guidewire as described above with reference to variousexemplary embodiments of the present invention. In step 2230, theguidewire is then removed. Further, in step 2240, the balloon isinflated, and imaging begins in step 2250.

FIGS. 28A-28C show exemplary steps of an operation which utilizes theexemplary arrangement of the present invention for imaging over an arealarger than the balloon length by multiple placements of the balloon.The imaging sets obtained with the balloon in positions shown in FIGS.28A-28C can be combined to yield imaging over a large area.

FIG. 29 shows an exemplary embodiment of a method for placement of animaging probe at the junction between the tubular esophagus and thestomach. FIGS. 30A-30C show the exemplary steps performed by theexemplary arrangement of the present invention using the method of FIG.29. In step 2400, the catheter is inserted with the balloon deflated andplaced in the stomach. In step 2410, the balloon is inflated (FIG. 30A),and in step 2420, pulled back until resistance is felt, thereby locatingthe proximal side of the balloon at the gastro-esophageal junction(junction between the stomach and esophagus). Next, in step 2430, theballoon is partially deflated (FIG. 30B), and the catheter is pulledback a predefined amount such as the balloon length. Further, in step2440, the balloon is inflated, and imaging proceeds with the catheterlocated at the gastro-esophageal junction (FIG. 30C).

In an additional exemplary embodiment of the present invention, theimaging system can be operated in an abbreviated imaging mode (e.g.,scout imaging) to determine if the catheter is properly located in theorgan. A full comprehensive imaging can begin after proper catheterplacement is confirmed. In yet another exemplary embodiment of thepresent invention, the balloon centering catheter can be inflated withmaterials that are optically transparent other than air such as but notlimited to water, heavy water (D₂O), or oil. In still another exemplaryembodiment of the present invention, the laser marking may utilizepreviously applied exogenous agents in the organ to provide absorptionof the marking laser. In a further exemplary embodiment of the presentinvention, a lubricating agent can be used to aid insertion of thecatheter. In another exemplary embodiment of the present invention, amucosal removal agent can be used prior to imaging to reduce mucous inthe organ which can reduce imaging quality.

The foregoing merely illustrates the principles of the invention.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.Indeed, the arrangements, systems and methods according to the exemplaryembodiments of the present invention can be used with and/or implementany OCT system, OFDI system, SD-OCT system or other imaging systems, andfor example with those described in International Patent ApplicationPCT/US2004/029148, filed Sep. 8, 2004, U.S. patent application Ser. No.11/266,779, filed Nov. 2, 2005, and U.S. patent application Ser. No.10/501,276, filed Jul. 9, 2004, the disclosures of which areincorporated by reference herein in their entireties. It will thus beappreciated that those skilled in the art will be able to devisenumerous systems, arrangements and methods which, although notexplicitly shown or described herein, embody the principles of theinvention and are thus within the spirit and scope of the presentinvention. In addition, to the extent that the prior art knowledge hasnot been explicitly incorporated by reference herein above, it isexplicitly being incorporated herein in its entirety. All publicationsreferenced herein above are incorporated herein by reference in theirentireties.

1-64. (canceled)
 65. An apparatus for determining a position on or in a biological tissue, comprising: at least one computer arrangement which is configured to: receive data associated with at least one information regarding at least one portion of the biological tissue, and based on the data, cause a visible change on or in at least location of the at least one portion using at least one electro-magnetic radiation.
 66. The apparatus according to claim 65, wherein the data in is image data, and wherein the at least one computer arrangement is configured to receive the image data obtained using an optical imaging technique.
 67. The apparatus according to claim 65, wherein the at least one computer arrangement is further configured to using image further data for the visible change on or in the at least one location, automatically effectuate at least one of a removal or a destruction of at least section of the at least one portion.
 68. The apparatus according to claim 67, wherein the image further data is visible image data.
 69. The apparatus according to claim 67, wherein the at least one arrangement is further configured to obtain the image further data after the visible change is effectuated.
 70. The apparatus according to claim 67, wherein the at least one image includes a volumetric image of the at least one portion.
 71. The apparatus according to claim 70, wherein the volumetric image is a cylindrical image having at least one (i) a diameter of between about 10 mm to 100 mm, or (ii) an extension of at most about 1 m.
 72. The apparatus according to claim 70, further comprising at least one further computer arrangement which is configured to receive the image further data, and guide a visualization to the at least one portion based on the image further data.
 73. The apparatus according to claim 65, wherein the at least one computer arrangement causes the visible change by ablating the at least one portion.
 74. The apparatus according to claim 73, wherein the ablation of the at least one portion is performed by irradiating the at least one portion with the at least one electro-magnetic radiation.
 75. The apparatus according to claim 66, wherein the optical imaging technique includes an optical coherence tomography.
 76. The apparatus according to claim 66, wherein the optical imaging technique includes a confocal microscopy technique.
 77. The apparatus according to claim 78, wherein the confocal microscopy technique is a spectrally-encoded confocal microscopy technique.
 78. The apparatus according to claim 65, wherein the optical imaging technique includes a confocal microscopy technique.
 79. The apparatus according to claim 65, wherein the at least one computer arrangement is situated in a probe, and further comprising an ablation radiation laser source arrangement provided in the probe which is controlled by the at least one computer arrangement to cause the visible change on or in the at least one portion.
 80. The apparatus according to claim 79, wherein the at least one computer arrangement is configured to obtain the at least one information via at least one wave-guiding arrangement, and the ablation radiation laser source arrangement provides the at least one electro-magnetic radiation via the at least one wave-guiding arrangement to cause the visible change.
 81. A method for determining a position on or in a biological tissue, comprising: with a computer, receiving data associated with at least one information regarding at least one portion of the biological tissue, and based on the first data, causing a visible change on or in at least location of the at least one portion using at least one electro-magnetic radiation
 82. The method according to claim 81, wherein the data in is image data, and wherein the image data is obtained using an optical imaging technique.
 83. The method according to claim 81, further comprising, using image further data for the visible change on or in the at least one location, automatically effectuating at least one of a removal or a destruction of at least section of the at least one portion.
 84. The method according to claim 83, wherein the image further data is visible image data. 